Glutathione has been implicated to play an important role in the maintenance of the clarity of lens by keeping the crystallins and membrane proteins in the reduced form. We have now introduced the use of two new compounds, t-butyl hydroperoxide and cumene hydroperoxide, to specifically oxidize lens GSH to GSSG. These reagents readily enter the lens and enzymatically oxidize GSH. Five millimolar t-butyl hydroperoxide (TBHP) has been found to oxidize 80 percent of rat lens GSH in about 5 minutes of 25 degrees. Evidence has been presented that a portion, 30 to 35 percent, of glutathione gets bound to lens proteins which can be cleaved of the proteins by glutathione reductase and NADPH in one step. Distribution of gamma-glutamyl transpeptidase in anatomical parts of human lens was found to be in the decreasing order from epithelium, cortex and nucleus. No significant decrease in gamma-glutamyl transpeptidase activity was observed in senile cataractous lenses. This enzyme has been partially purified from human cultured lens epithelium. Human lens gamma-glutamyl transpeptidase was found to be under the same genetic control as the kidney, liver and skin fibroblast enzymes. This enzyme has been purified to homogeneity from human kidney. Physiological levels of copper (50 micromoles) almost completely inhibited the following enzymes in human and bovine lens homogenates: hexokinase, phosphofructokinase, pyruvate kinase, glyceraldehyphosphate dehydrogenase, phosphoglycerate kinase, 6-phosphogluconate dehydrogenase, aldolase and glucose-6-P dehydrogenase. The inhibition was not significantly reversed by EDTA or by dialysis of the copper-treated enzyme against phosphate buffer. Similar results were obtained when human cultured lens epithelium was used as the enzyme source. The studies indicated that if the increased amount of copper present in senile cataractous lenses is in the free form, it can significantly impair glucose metabolism in the lens. Effect of selenium deficiency on increased susceptibility to cataract formation is being studied. BIBLIOGRAPHIC REFERENCE: Miller, Steven P., Dharmendra V. Arya and Satish K. Srivastava. (1976) Studies of gamma-glutamyl transpeptidase in human ocular tissues. Exp. Eye Res. 22:329.